Proof-of-Concept Study of MSP3-LSP Vaccine to Protect Against Malaria in Africa

NCT01341704 | Completed Phase 2 DMC

• 1 other identifier: MMVDU-013
• Study Type: interventional
• Target: 800
• Locations: 1 country
• Sites: 1

Brief Summary

Hypothesis: The MSP3-LSP/Alum vaccine, administered to children will have a protective efficacy of at least 30% (lower bound of confidence interval of 0) against malaria disease occurring during a period beginning from 14 days after the 3rd immunization until 1 year after. The primary objective of this double-blind, randomized, controlled trial will be to assess the clinical efficacy of MSP3-LSP/AlOH vaccine when administered by subcutaneous route in children aged 12-48 months against all clinical malaria episodes occurring during a period beginning from 14 days after the 3rd immunization until 3 months after 3rd immunization, when administered according to the following schedule:- Primary administration: Three doses of administered 4 weeks apart Secondary administration (Boost): One dose 3 months after the third dose in year 1 of the trial; and two doses, given exactly one year after the date corresponding to the third dose and the first boost given during Year 1 Case definition for an episode of malaria is a febrile illness with axillary temperature of ≥ 37.5ºC with P. falciparum parasitemia ≥ 5000 per μL

Conditions

Malaria

Keywords

malaria; vaccine; clinical trials; proof of concept; efficacy

Outcome Measures

Primary Outcomes (1)

• Number of episodes of clinical malaria occurring during a period beginning from 14 days after the 3rd immunization until 3 months after 3rd immunization in all subjects.

  A clinical malaria episode is defined as a febrile illness with a documented axillary temperature of

  3 months

Secondary Outcomes (3)

• Number of subjects with solicited adverse events

  7 days following each vaccination

• Number of subjects with unsolicited adverse events

  30 days following each vaccination

• Number of subjects with serious adverse events

  2 years

Study Arms (2)

MSP3-LSP/AlOH

EXPERIMENTAL

Synthetic polyprotein of 96 amino acids (186-276 in 3D7 strain) manufactured by solid-phase synthesis by SYNPROSIS, France; lyophilized product was formulated extemporaneously with aluminum hydroxide (Reheis). 30 microgram per dose; three dose schedule on study day 0, 28 and 56 for primary series

Biological: MSP3-LSP/AlOH

Control

PLACEBO COMPARATOR

Primary series: Verorab Rabies vaccine; Secondary/Booster series: 0.9% NaCL/Normal Saline

Biological: Verorab Vaccine; Other: 0.9% NaCl/Normal Saline

Interventions

MSP3-LSP/AlOH BIOLOGICAL

30 µg of test vaccine MSP3-LSP/AlOH, administered by subcutaneous route according to the following schedule:- Primary administration: Three doses administered at 4 weeks interval: D0, D28 (± 2 days), D56 (± 4 days) Secondary administration (Boost): Year 1: One dose 3 months after the third dose Year 2: Two doses, given exactly one year after the date corresponding to the third dose and the first boost given during Year 1

MSP3-LSP/AlOH

Verorab Vaccine BIOLOGICAL

The Verorab rabies vaccine will be given as control for the primary series of the experimental vaccine. It consists of inactivated rabies virus produced in vero cells (Wistar Rabies PM/W138 1503-3M (inactivated). Manufacturer SANOFI PASTEUR SA. Presentation is 0.5 ml per dose in a pre-filled syringe.

Control

0.9% NaCl/Normal Saline OTHER

0.5 ml per dose; to be given as control for the secondary/booster doses of experimental vaccine

Control

Eligibility Criteria

• Age: 12 Months - 48 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Children aged 12-48 months old
• Healthy by medical history, physical examination and laboratory investigation
• Signed/thumb printed informed Consent by guardian/parent
• Resident in the study area villages during the whole trial period

You may not qualify if:

• Symptoms, physical signs of disease that could interfere with the interpretation of the trial results or compromising the health of the subjects
• Immunosuppressive therapy (steroids, immune modulators or immune suppressors) within 3 months prior recruitment. (for corticosteroids, this will mean prednisone, or equivalent, ≥ 0.5 mg/kg/day. Inhaled and topical steroids are allowed.)
• Cannot be followed for any social, psychological or geographical reasons.
• Use of any investigational drug or vaccine other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use up to 30 days after the third dose.
• Suspected or known hypersensitivity to any of the vaccine components or to previous vaccine.
• Laboratory abnormalities on screened blood samples.
• Planned administration of a vaccine not foreseen by the study protocol within 30 days before the first dose of vaccine. An exception, is the receipt of an EPI or licensed vaccine (measles, oral polio, Hib, meningococcal and combined diphtheria/pertussis/tetanus vaccines) which may be given 14 days or more before or after vaccination
• Evidence of chronic or active hepatitis B or C infection
• Presence of chronic illness that, in the judgment of the investigator, would interfere with the study outcomes or pose a threat to the participant's health.
• Administration of immunoglobulin and/or any blood products within the three months preceding the first dose of study vaccine or planned administration during the study period
• History of surgical splenectomy.
• Moderate or severe malnutrition at screening defined as weight for age Z-score less than 2

Sponsors & Collaborators

• Vac4All: lead
• University of Bamako: collaborator

Study Sites (1)

Malaria Research and Training Center Department of Epidemiology of Parasitic Diseases Faculty of Medicine, Pharmacy and Dentistry University of Bamako BP 1805, Point G Bamako, Mali, West Africa Tel/Fax 223-2022-8109

Bamako, 1805, Mali

Location

MeSH Terms

Conditions

Malaria

Interventions

Saline Solution

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Mahamadou Sissoko, MD

  Malaria Research and Training Center Department of Epidemiology of Parasitic Diseases Faculty of Medicine, Pharmacy and Dentistry University of Bamako BP 1805, Point G Bamako, Mali, West Africa

  PRINCIPAL INVESTIGATOR

• Pierre L Druilhe, MD

  CEO, Vac4All

  STUDY DIRECTOR

• Ogobara Doumbo, MD

  Chief, MRTC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2011
• First Posted: April 26, 2011
• Study Start: May 1, 2011
• Primary Completion: December 1, 2011
• Study Completion: March 1, 2013
• Last Updated: August 31, 2015

Record last verified: 2015-08

Locations

MA (1)